Systemic inhibition of nitric oxide and prostaglandins in volume-induced natriuresis and hypertension.
Nitric oxide (NO) synthesis inhibition with NG-nitro-L-arginine methyl ester (L-NAME) (10 micrograms.kg-1.min-1 i.v.), cyclooxygenase inhibition with meclofenamate (Meclo; 5 mg/kg i.v. bolus), and combination of drugs (L-NAME + Meclo) were used to investigate the roles of NO and prostaglandins (PG) in the hemodynamic and natriuretic responses to isotonic saline volume expansion (VE; 5% body wt over 60 min) in anesthetized dogs. Before VE, L-NAME (n = 6), Meclo (n = 6), and L-NAME + Meclo (n = 6) produced significant increments in mean arterial pressure (MAP) of 12 +/- 2, 15 +/- 3, and 17 +/- 3 mmHg, respectively. VE did not change MAP in Meclo-treated dogs, but produced a significant elevation in the control dogs (14 +/- 6 mmHg), in L-NAME-treated dogs (17 +/- 6 mmHg), and in dogs pretreated with L-NAME + Meclo (12 +/- 5 mmHg). VE alone induced marked natriuretic responses in the control (38 +/- 9 to 562 +/- 86 mumol/min), L-NAME (31 +/- 9 to 664 +/- 65 mumol/min), and Meclo groups (41 +/- 10 to 699 +/- 51 mumol/min). However, this natriuretic response was attenuated in dogs pretreated with L-NAME + Meclo (12 +/- 4 to 185 +/- 52 mumol/ min). These results indicate that 1) blockade of both NO and PGs has significant diminishing effects on volume-induced natriuresis, 2) NO blockade alone impairs volume-induced natriuresis in a manner that requires further increases in MAP to restore the natriuresis, and 3) PG blockade alone does not curtail volume-induced natriuresis.
Krier
J D
JD
Department of Physiology and Biophysics, Mayo Medical School, Rochester, Minnesota 55905, USA.
Romero
J C
JC
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011453:Prostaglandins / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D012462:Saline Solution, Hypertonic; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester